The underlying mechanisms indicating an association between minimal to moderate endometriosis and infertility are not clearly understood. Recent investigations have focused on the presence of an aseptic inflammation of the peritoneal cavity, resulting in a distortion of the normal function of the pelvic organs, as an important contributory mechanism. Other proposed causes for reproductive failure in the less severe cases of endometriosis include oligoanovulation, luteal phase defects, and luteinized unruptured follicle syndrome. However, these suggestions need to be clearly substantiated and each one cannot be considered the sole cause of infertility in patients with endometriosis. Other factors, which include alterations in the sperm-egg interaction with possible phagocytosis of the sperm or interference with early embryo development, may be taken into consideration when studying the associated infertility of these patients. The biochemical modifications that have been described in endometriosis include an increase in the concentration of prostaglandins, cytokines and complement components in the peritoneal fluid and activation of resident macrophages. Halme J, et al., Am J Obstet Gynecol 1983 145:333 and Hill J A, et al., Am J Obstet Gynecol 1989 161:861. The activation of leukocytes within the peritoneal cavity is evidenced by cytoskeletal rearrangement of the cells and by changes in the lipid metabolism with activation of protein kinases or release of lysosomal enzymes.
The role of peritoneal fluid in the physiologic modifications of the peritoneal cavity of patients who otherwise would seem to have a normal pelvic environment has been studied. Endometriosis without severe anatomic distortion is associated with an increase in the peritoneal fluid volume, cell number, and concentration of lysosomic enzymes as compared with normal fertile controls. The peritoneal fluid arises primarily from two different sources: the plasma as a transudate and the ovary as an exudate; other sources are tubal fluid; retrograde menstruation, and secretions from the macrophages in the cavity. However, the exact source for the biochemical modifications observed in endometriosis is not clear.
Normally the peritoneal fluid contains several types of blood cells, with macrophages and lymphocytes being the most abundant; desquamated endometrial and mesothelial cells are also present. This cellular composition is modified in patients with endometriosis. Badaway S. Z., et al., Fertil Steril 1984 42:704. Several theories exist regarding the mechanisms responsible for these alterations, one of which is considered by the present invention--the presence of a chemotactic stimulus that would attract more cells into the peritoneal cavity, or alternatively, activate and induce proliferation of resident macrophages in response to these unknown factors.
Therefore to study the modifications seen within the pelvic cavity in endometriosis investigators have focused on the initial stages of the disease in which active endometrial glands and stroma are present and are clearly associated with changes in the peritoneal fluid. Some of the modifications include an increase in the concentrations of cytokines and the production of various growth factors by the infiltrating leukocytes. The contribution of these factors to the inflammatory changes of the peritoneal fluid is yet to be determined. Fakih H, et al., Fertil Steril 1987 47:213 and Halme J, et al., J Clin Endocrinol Metab 1988 66:1044.
The role of the peritoneal fluid of patients with minimal to moderate endometriosis was examined in the present invention as a contributor to the inflammatory changes observed in the pelvic cavity of these patients. Leiva, M., et al., Am J Obstet and Gynecol 1993 168:592. In this regard, the chemotactic potential of peritoneal fluid obtained from patients with minimal to moderate endometriosis was investigated. Responsive cells included neutrophils isolated from peripheral blood or HL60-C15-differentiated neutrophils and macrophages derived from U937 cells. These findings were compared with the activity observed in normal patients or patients undergoing medical treatment for this condition.
These results determine the potential of the invention to satisfy the great needs in the art of diagnosis and treatment of endometriosis. Accurate and early methods of detection of endometriosis are needed such that methods of treatment may begin promptly.